J. Org. Chem. 1981,46, 1025-1026 1.23 ( ~ , H, 3 CH3), 1.02 ( ~ , H, 3 CHJ, 0.80 (d, 3 H, J = 7 Hz, C(4) methyl). An analytical sample was prepared by recrystallization from ether; mp 161-163 OC. Anal. Calcd for C22H308: C, 69.81; H, 9.05. Found: C, 69.78; H, 8.98.
1025 Scheme I
-
Me,N
Me,+,CCI2
X2@
Acknowledgment. This investigation was supported by a Public Health Service Research Grant (CA 28865) from the National Cancer Institute. G.V. is grateful to the Consiglio Nazionale delle Ricerche d'Italia for a fellowship.
x3
x4
aq. NaOH
-
Xd
1
Registry No. 1, 75935-29-4; 2, 75924-48-0; 4, 76156-58-6; 5, 76156-59-7;6,76156-60-0; 7,76156-61-1; 8,76156-62-2; 9,76156-63-3; 10,76189-75-8; 12,76156-64-4; 13 (R = H), 76156-65-5; 13 (R = Me), 76156-66-6.
(+ MeN =CCI2 )
3
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755 Received October 8, 1980
Arenimines are useful polycyclic aromatic hydrocarbon synthetic equi~alents.'-~Previously, we' and others2Jhave into the transformed N-alkyl-1,4-dihydroaren-l,44mines corresponding aromatic hydrocarbons using mild oxidizing conditions (usually m-chloroperbenzoic acid), a reaction that may involve cheletropic extrusion4of a nitrosoalkane from the derived arenimine oxide. We now report that dichlorocarbene, generated under phase-transfer conditions by using the Makosza method: efficiently converts 9-methyl-l,4-dihydronaphthalen-1,4imines ( 1) and 11-methyl-1,2,3,4-tetrachloro-9,lO-dihydroanthracen-9,lO-imine( 5 ) to the corresponding naphthalenes (3, Scheme I) and 1,2,3,4-tetrachloroanthracene (6, Scheme 11), respectively. Our results are summarized in Table I. By comparison, the peracid oxidation of naphthalenimines'~~ proceeds in 66-94% yield, and the peracid or hydrogen peroxide oxidation of anthracenimines' proceeds in 26-92% yield. As suggested by the stereospecific fragmentation of aziridinium ylides (generated also from carbenes and aziridines) ,6 the present reaction pathway may involve ammonium ylide 2 which suffers rapid cheletropic loss4of methyl isocyanide dichloride (4: not isolated)8to furnish the arene.g The requisite arenimines 1 and 5 were prepared by a Diels-Alder reaction between the appropriate benzyne and either N-methylpyrrole or N-methylisoindole,respectively. (1) G. W. Gribble, R. W. Allen, P. S. Anderson, M. E Christy, and C. D. Colton, Tetrahedron Lett., 3673 (1976). (2) A. Sy and H. Hart, J . Org. Chem., 44, 7 (1979). (3) H. Hart and A. Teuerstein, Synthesis, 693 (1979). (4) R. B. Woodward and R. Hoffmann, "The Conservation of Orbital Symmetry", Verlag Chemie, Weinheim/Bergstr., Germany, 1970, pp 152-163. (5) M. Makosza and M. Wawrzyniewicz, Tetrahedron Lett., 4659 (1969). (6) Y. Hato and M. Watanabe, Tetrahedron Lett., 3827 (1972). (7) E. Kdhle, B. Anders, and G. Zumach, Angew. Chem., Znt. Ed. Engl., 6,649 (1967). (8) We have made no attempt to ascertain the fate of 4, but, presumably, it is hydrolyzed to methylamine and carbonate under the reaction conditions. (9) We and others1° have found that the methiodides of arenimines fragment to aromatic hydrocarbons upon treatment with base (KOH, MeMgI) or simply on standing for extended periods. These reactions may also involve ammonium ylide intermediates. (10) P. S. Anderson (Merck Sharp and Dohme Research Laboratories), private communication.
0022-3263/81/1946-1025$01.25/0
4
Scheme I1
Dichlorocarbene-Induced Deamination of Naphthalen- l,4-imines and Anthracen-9,lO-imines Gordon W. Gribble,* Robert W. Allen, Craig S. LeHoullier, Jefferson T. Eaton, N. Roy Easton, Jr., Robert I. Slayton, and Mukund P. Sibi
J
2
.,,Me CI
CI
-
aq. NoOH
C -.I
CI
6
5
The benzynes were generated by treating a polyhalobenzene with n-butyllithium and effecting either halogen-lithium exchange (e.g., chloropentafluorobenzene, hexachlorobenzene, and trichlorotrifluorobenzene) or lithiation (e.g., 1,2,4,5-tetrachlorobenzene). The syntheses of lb-d and 5 have not been previously described and are presented in the Experimental Section. In summary,the dichlorocarbene-induced deamination of arenimines is a convenient alternative method to the oxidative deamination procedure'-3 and avoids use of the moderately expensive m-chloroperbenzoic acid. Experimental Section Melting points were obtained with a Mel-Temp Laboratory Devices apparatus in open capillary tubes and are uncorrected. Microanalyses were determined by PCR, Inc., or by Atlantic Microlab, Inc. Infrared spectra were measured with a PerkinElmer 137 or 599 instrument, and NMR spectra were obtained with a Perkin-Elmer R-24 spectrometer. Wwlm alumina was used for column chromatography and silica gel G (Merck) was used for TLC. Mass spectra were determined at 70 eV on a Finnigan 4023 GC/MS system by C. R. Hill and R. M. Soll. 9-Methyl-5,6,7,8-tetrafluoro-1,4-dihydronaphthalen-l,4imine (la). To a magnetically stirred solution of chloropentafluorobenzene (15 g, 0.074 mol) in dry EhO (250 mL) under N2 at -78 "C was added dropwise via syringe n-butyllithium (1.6 M in hexane; 50 mL, 0.080 mol). The solution was stirred for 30 min at -78 OC and then was treated with freshly distilled N methylpyrrole (8 g, 0.1 mol) dropwise at -78 O C . The resulting golden yellow solution was allowed to warm slowly to room temperature overnight. The mixture was treated with H 2 0 (50 mL) and then extracted with 6 N HCI. The acidic extract was cooled in an ice bath, basified with 50% aqueous NaOH, and extracted with CH2C12.Rotary evaporation of the water-washed and dried (Na2S04)extract gave 10.3 g of crude la as a brown solid which was sublimed at 80 "C (0.5 torr) to give 7.7 g (46%) of la as colorless crystals: mp 77-78 OC (lit." mp 75-76 "C); 'H NMR (CDC13)6 2.2 (8,3 H), 4.9 (m, 2 H), 6.9 (m, 2 H); IR (CHC13)2950 (s), 1490 (s), 1480 (s) 1295 (m), 1270 (m), 1110 (m), 1080 (m), 1040 (s),930 cm-' (m); mass spectrum,m / e (relative intensity) 229 (26), 214 (lo), 203 (loo), 188 (46),174 (14), 169 (19), 161 (33), 151 (29), 123 (16), 105 (12), 99 (18), 42 (96). 9-Methyl-5,6,7,8-tetrachlorolI4-dihydronaphthalen-1,4imine (lb). To a magnetically stirred slurry of hexachlorobenzene (38 g, 0.13 mol) (recrystallizedfrom EtOH) in dry EhO (1500 mL) (11) D. D. Callander, P. L. Coe, J. C. Tatlow, and A. J. Uff, Tetrahedron, 25, 25 (1969), prepared la from pentafluorobenzene in a similar manner to that described herein.
0 1981 American Chemical Society
J. Org. Chem. 1981,46, 1026-1030
1026
Table I. Deamination of Arenimines t o Arenes with Dichlorocarbene arenimine l a (Xl-4 = F) l b ( X l q 4= C1) IC( X , , 3 = F; X, = C1 I d ( X l , 2 , 4= C1; k3= H) 5
arene
mp,"C 108-110 199-200 104-106 91-92 209-210
3a 3b 3~
3d 6
yield, 5% 85 84 90 85 73
under N2 at -50 "C was added dropwise over 30 min n-butyllithium (2.25M in hexane; 59 mL, 0.13mol). The light yellow solution was allowed to warm to -35 "C and was then stirred at -35 to -25 "C for 1 h. Then freshly distilled N-methylpyrrole (22g, 0.27mol) was added in one portion, and the mixture was allowed to warm slowly to room temperature overnight. The reaction mixture was cooled to 0-5 "C and extracted with cold 4 N HC1. The acidic extract was cooled, basified with NaOH (pellets), and extracted with CHC13. The CHC13 extract was washed with H20,dried (KZCO,), and evaporated in vacuo to give crude l b as a white solid. Crystallization from MeOH-EhO gave 11 g (29%) of l b as colorless flakes in two crops, mp 155-156 "C. A second crystallization gave the analytical sample: mp 156-157 "C; 'H NMR (CDC1,) 8 2.2 (s, 3 H),4.8 (m, 2 H),7.0(m, 2 H); IR (CHCl,) 2955 (s), 1350 (s), 1300 (a), 1270 (m), 1160 (m), 1115 (s), 915 (m), 850 (m), 690cm-' (9); mass spectrum, m/e (relative intensity) 295 (22),269 (73),254 (12),217 (lo), 194 (ll), 181 (6), 160 (3),147 (3), 120 (6),98 (a), 42 (100). Anal. Calcd for CllH7NC&: C, 44.78;H, 2.40;N 4.75;C1,48.07. Found: C, 44.69;H, 2.38;N, 4.81;C1, 48.35. 9-Methyl-5,7-dichloro-6,8-difluoro-1 , a - d i h y d r o naphthalen-l,a-imine (IC). To a magnetically stirred solution (16.8g, 0.071 mol) in dry of 1,3,5-trichloro-2,4,6-trifluorobenzene EGO (250mL) under N2 a t -78 "C was added dropwise n-butyllithium (1.6M in hexane; 45 mL, 0.072mol). The solution was stirred for 1 h at -78 "C, treated at -78 "C over 30min with freshly distilled N-methylpyrrole (15g, 0.19mol), and then stirred at -78 "C for 1 h. The mixture was then allowed to warm slowly to room temperature overnight. The usual workup gave 10.9g (59%) of crude product which was distilled to afford IC as a colorless, low-melting solid mp 41-42 "C; bp 95-96 "C (0.35 torr). Redistillation gave the analytical sample: bp 109 "C (0.25torr); 'H IR (CHCI,) NMR (CDCl,) 6 2.2(s,3H),4.8(m, 2 H), 6.9(s,2H); 2955 (s),1460 (s), 1435 (s), 1410 (s), 1295 (m), 1150 (m), 1110 (m), 1060 (s), 870 (m), 840 (m), 810 cm-' (a); mass spectrum, m/e (relative intensity) 261 (6),235 (19),219 (5),185 (4),162 (7),149 (5),123 (4),99 (4),80 (a), 42 (100). Anal. Calcd for CllH7NF2Cl2: C, 50.41;H,2.69;N, 5.35;C1, 27.06. Found: C, 50.41;H, 2.73;N, 5.30;C1, 26.92. 9-Methyl-5,6,8-trichloro-1,4-dihydronaphthalen-l,4-imine (la). To a magneticallystirred slurry of 1,2,4,5-tetrachlorobenzene (21.6g, 0.10mol) in dry EGO (600mL) under N2 at -50 "C was added dropwise over 40 min n-butyllithium (2.28M in hexane; 44 mL, 0.10mol). The solution was stirred for an additional 35 min at -50 "C and then treated dropwise over 10min with freshly distilled N-methylpyrrole (7.8g, 0.096mol). The solution was stirred at -50 to -35 "C for 5.5 h and then allowed to warm to room temperature overnight. The mixture was cooled to 0 "C and then treated slowly with cold 4 N H 8 0 4(150mL). The EhO layer was separated and discarded. The acid layer was extracted with several portions of Et20 (discarded), cooled to 0 "C, and basified with cold 4 N NaOH. Extraction with EhO followed by drying (K,CO,) and concentration in vacuo afforded 11.6g (46%) of crude Id as a brown oil which crystallized in a freezer. Sublimation a t 0.5 torr gave 6.85g (27%) of pure Id: mp 58-59.5 "C; 'H NMR (CDCl,) 6 2.2(s, 3 H), 4.8(m, 2 H), 7.0(m, 2 H), 7.1 (s, 1 H); IR (CHC1,) 2960 (s), 1420 (s), 1315 (m), 1300 (m), 1275 (m), 1155 (m), 1110 (s), 860 (m), 850 (m), 710cm-' (m);mass spectrum, m/e (relative intensity) 259 (31,233 (13),217 (2),183 (41,160 (5), 147 (4),123 (3), 109 (3),98 (7),80 (9),42 (100). Anal. Calcd for CllH,,JC13: C, 50.71;H, 3.09;N,5.38;C1,40.82. Found: C, 50.76;H, 3.14;N,5.45;C1, 40.85. 1l-Methyl- 1,2,3,4-tetrachloro-9,lO-dihydroanthracen9,lO-imine (5). This was prepared from hexachlorobenzene and 2-methyli~oindole'~ by using the procedure described for l b to
give 5 as colorless crystals: mp 163 "C, after crystallization from acetone; 'H NMR (CDC1,) 6 2.3 (s, 3 H), 5.2(8, 2 H), 7.1 (m, 2 H), 7.4(m, 2 H); IR (KBr) 2830 (m), 1355 (s),1290 (m), 1260 (m), 1220 (m), 1090 (s), 795 (m), 730 cm-l ( 8 ) ; mass spectrum, m/e (relative intensity) 345 (29),330 (lo), 316 (14),310 (E) 308 , (E), 282 (13),280 (15),246 (lo), 174 (a), 91 (17),42 (100). Anal. Calcd for C1J3HyC&: C, 52.21;H, 2.63;N, 4.06. Found; C, 53.05;H, 3.26;N, 4.11. General Deamination Procedure. To a magnetically stirred in CHC1, (25mL) at room temsolution of arenimine (2"01) perature under N2 was added 50% aqueous NaOH (3mL) and benzyltriethylammonium chloride (0.2 mmol). The resulting mildly exothermic reaction was stirred at ambient temperature overnight and then was partitioned between 3 N HCl (35mL) and CHC1, (50 mL). The organic layer was water washed, dried (Na804),and concentrated in vacuo to afford the crude product which was purified as described below. Where possible the products were compared (TLC, Et,NMR)with those compounds prepared in our earlier study' or with commercial samples. 1,2,3,4-Tetrafluoronaphthalene(3a). The crude product was recrystallized from hexane to give 3a: 85% yield; mp 108-110 "C (lit.', mp 11O-111 "C). 1,2,3,4-Tetrachloronaphthalene(3b). The crude product was recrystallized from CHC1, to give 3 b 84% yield; mp 199-200 "C (lit." mp 198 "C). 1,3-Dichloro-2,4-difluoronaphthalene(3c). The crude product was sublimed a t 80"C (0.5 torr) to give 3c: 90% yield; mp 103-104 "C (lit.lS mp 103-104 "C). 1,2,4-Trichloronaphthalene(3d). The crude product was sublimed at 80 "C (0.5 torr) to give 3d: 85% yield; mp 91-92"C (lit.16 mp 92 "C). 1,2,3,4-Tetrachloroanthracene(6). The crude product was recrystallized from MeOH-CHCl, (1:l) to give 6 73% yield; mp 209-210 "C (lit.17 mp 217-219 "C).
Acknowledgment. This investigation was supported by Grant No. CA-14968 and CA-24422, awarded by the National Cancer Institute, DHEW. We also thank Merck Sharp and Dohme Research Laboratories and The Lilly Research Laboratories for their support of our research program and Dr. N. Ishikawa (Tokyo Institute of Technology) for a generous sample of 1,3,5-trichloro-2,4,6-trifluorobenzene. Registry No. la, 5875-75-2; lb, 26477-20-3; IC, 76137-28-5; Id, 76137-29-6; 3a, 711-55-7; 3b, 20020-02-4; 3c, 27508-76-5; 3d, 5040251-2;5, 76137-30-9; 6, 25283-02-7; chloropentafluorobenzene,34407-0;N-methylpyrrole, 96-548; hexachlorobenzene,118-74-1; 1,3,5trichloro-2,4,6-trifluorobenzene, 319-88-0; 1,2,4,5-tetrachlorobenzene, 95-94-3; 2-methylisoindole,3380484-1; dichlorocarbene, 1605-72-7. (12)D.L.Garmaise and A. Ryan, J.Heterocycl. Chem., 7,413(1970). (13)P. L.Coe, R. Stevens, and J. C. Tatlow, J. Chem. SOC.,3227 (1962). (14)J. v. Braun, Ber. Dtsch. Chem. Ges., 56, 2332 (1923). (15)S.Hayashi and N. Ishikawa, Chem. Abstr., 73, 45241 (1970). (16)P.T.Cleve, Ber. Dtsch. Chem. Ges., 21, 893 (1888). (17)J. Fort, F.Serratosa,and L. Vilarrasa, Tetrahedron Lett., 4105 (1970).
Nucleophilic Aromatic Substitution Reaction of Some 3-Nitroimidazo[ 1,2-a]pyridines with T h i o g l y c o l a t e Anion in DMF Jean-Claude Teulade,* Ggrard Grassy, Roger Escale, and Jean-Pierre Chapat Laboratoire de Chimie Organique Pharmaceutique, Facult6 de Pharmacie, 34060 Montpellier-Cedex, France Received August 5, 1980
Imidazo[ 1,2-a]pyridines 1 undergo nucleophilic' and electrophilic2aromatic substitution reactions. Only a few
0022-3263/81/1946-1026$01.25/0 -, , 0 1981 American Chemical Society I
~
